Regulation of Integrin Adhesions by Varying the Density of Substrate-Bound Epidermal Growth Factor

Biointerphases

article

Tamar Shahal¹  Benjamin Geiger¹  Iain E. Dunlop²  Joachim P. Spatz³ 

[1] Department of Molecular Cell Biology, Weizmann Institute of Science;Department of Materials, Imperial College London;Department for New Materials and Biosystems, Max-Planck-Institute for Intelligent Systems;Department of Biophysical Chemistry, Institute for Physical Chemistry, University of Heidelberg

关键词: Epidermal Growth Factor Receptor;    Epidermal Growth Factor;    A431 Cell;    Focal Adhesion;    Actin Stress Fiber;   

DOI  :  10.1007/s13758-012-0023-0

学科分类：基础医学

来源: SpringerOpen

【 摘 要 】

Substrates coated with specific bioactive ligands are important for tissue engineering, enabling the local presentation of extracellular stimulants at controlled positions and densities. In this study, we examined the cross-talk between integrin and epidermal growth factor (EGF) receptors following their interaction with surface-immobilized Arg-Gly-Asp (RGD) and EGF ligands, respectively. Surfaces of glass coverslips, modified with biotinylated silane-polyethylene glycol, were functionalized by either biotinylated RGD or EGF (or both) via the biotin–NeutrAvidin interaction. Fluorescent labeling of the adhering A431 epidermoid carcinoma cells for zyxin or actin indicated that EGF had a dual effect on focal adhesions (FA) and stress fibers: at low concentrations (0.1; 1 ng/ml), it stimulated their growth; whereas at higher concentrations, on surfaces with low to intermediate RGD densities, it induced their disassembly, leading to cell detachment. The EGF- dependent dissociation of FAs was, however, attenuated on higher RGD density surfaces. Simultaneous stimulation by both immobilized RGD and EGF suggest a strong synergy between integrin and EGFR signaling, in FA induction and cell spreading. A critical threshold level of EGF was required to induce significant variation in cell adhesion; beyond this critical density, the immobilized molecule had a considerably stronger effect on cell adhesion than did soluble EGF. The mechanisms underlying this synergy between the adhesion ligand and EGF are discussed.

【 授权许可】

CC BY